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在胰腺导管腺癌患者中,循环 Th17 细胞群体增加。

Increased circulating Th17 cell populations in patients with pancreatic ductal adenocarcinoma.

机构信息

Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, 110029, Ansari Nagar, New Delhi, India.

Department of Gastrointestinal Surgery, All India Institute of Medical Sciences, New Delhi, India.

出版信息

Immunogenetics. 2023 Oct;75(5):433-443. doi: 10.1007/s00251-023-01318-4. Epub 2023 Aug 4.

Abstract

T-helper 17 (Th17) cells are a subset of CD4 helper T cells that produce interleukin 17 (IL-17) and play a crucial role in the pathogenesis of inflammatory and autoimmune diseases. Few studies have been conducted to determine the role of Th17 cells in the tumorigenesis and development of pancreatic ductal adenocarcinoma (PDAC); however, its role is still unclear. In this study, the percentage of circulating Th17 cells and serum levels of IL-17A and IL-23 were analyzed using flow cytometry and ELISA, respectively, in 40 PDAC patients, 30 chronic pancreatitis (CP) patients and 30 healthy controls (HC). In addition, the mRNA expression levels of IL-17A, STAT3 and RORγt in tissue samples were quantified by qRT-PCR. The results showed that the percentage of circulating Th17 cells and the concentrations of serum IL-17A and IL-23 were significantly increased in PDAC patients as compared to CP and HC (P < 0.001). In addition, the higher level of IL-17A was significantly correlated with the poor overall survival of the PDAC patients. Furthermore, the frequencies of Th17 cells and IL-17A were significantly higher in stage III+IV PDAC patients versus stage I+II. A significant increase in IL-17A, STAT3 and RORγT mRNA was observed in patients with PDAC. Taken together, these findings suggest that the increased circulating Th17 cells and serum IL-17A may be involved in the development and metastasis of PDAC, and thus represent potential targets for the treatment of PDAC.

摘要

辅助性 T 细胞 17(Th17)细胞是 CD4 辅助性 T 细胞的一个亚群,其能产生白细胞介素 17(IL-17),并在炎症性和自身免疫性疾病的发病机制中发挥关键作用。虽然已有一些研究旨在确定 Th17 细胞在胰腺导管腺癌(PDAC)的发生和发展中的作用,但该作用仍不清楚。在这项研究中,我们通过流式细胞术分析了 40 名 PDAC 患者、30 名慢性胰腺炎(CP)患者和 30 名健康对照者(HC)的循环 Th17 细胞的百分比,以及通过 ELISA 分别分析了血清中 IL-17A 和 IL-23 的水平。此外,通过 qRT-PCR 对组织样本中 IL-17A、STAT3 和 RORγt 的 mRNA 表达水平进行了定量分析。结果显示,与 CP 和 HC 相比,PDAC 患者的循环 Th17 细胞百分比以及血清 IL-17A 和 IL-23 的浓度均显著升高(P<0.001)。此外,IL-17A 水平越高,PDAC 患者的总体生存率越低。此外,III+IV 期 PDAC 患者的 Th17 细胞和 IL-17A 水平显著高于 I+II 期。在 PDAC 患者中,IL-17A、STAT3 和 RORγT mRNA 的表达水平均显著增加。综上所述,这些发现表明,循环 Th17 细胞和血清 IL-17A 的增加可能与 PDAC 的发展和转移有关,因此代表了 PDAC 治疗的潜在靶点。

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